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One-step 18F-labeling of peptides for positron emission tomography imaging using the SiFA methodology

Nature Protocols volume 7, pages 1946–1955 (2012)Cite this article

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Abstract

Here we present a procedure to label peptides with the positron-emitting radioisotope fluorine-18 (18F) using the silicon-fluoride acceptor (SiFA) labeling methodology. Positron emission tomography (PET) has gained high importance in noninvasive imaging of various diseases over the past decades, and thus new specific imaging probes for PET imaging, especially those labeled with 18F, because of the advantageous properties of this nuclide, are highly sought after. N-terminally SiFA–modified peptides can be labeled with 18F− in one step at room temperature (20–25 °C) or below without forming side products, thereby producing satisfactory radiochemical yields of 46 ± 1.5% (n = 10). The degree of chemoselectivity of the 18F-introduction, which is based on simple isotopic exchange, allows for a facile cartridge-based purification fully devoid of HPLC implementation, thereby yielding peptides with specific activities between 44.4 and 62.9 GBq μmol−1 (1,200–1,700 Ci mmol−1) within 25 min.

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Figure 1: 18F-Labeling of peptides using SiFA.
Figure 2: Influence of the amount of oxalic acid on the radiochemical yield of peptide labeling with 18F− (labeled peptide = SiFA-Aoa-Tyr3-TATE).
Figure 3: 18F-Labeling of SiFA-Aoa-Asn(AcNH-β-Glc)-(Asp)2-PEG-Tyr3-octreotate.
Figure 4: HPLC chromatogram of SPE-purified [18F]SiFA-Aoa-Asn(AcNH-β-Glc)-(Asp)2-PEG-Tyr3-octreotate ([18F]5).

Change history

  • 23 October 2012

     In the version of this article initially published online, Katy Orchowski's name was spelled incorrectly. The surname Orchovski has been corrected to read Orchowski. The error has been corrected in all versions of this article.

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Acknowledgements

We thank the cyclotron crew of the McConnell Brain Imaging Centre for providing fluorine-18. The financial support of the following grant agencies is gratefully acknowledged: Canada Foundation for Innovation (CFI) project no. 203639 to R.S., Natural Sciences and Engineering Research Council of Canada (NSERC) Strategic Project Grant Program (STPGP) no. 412893 to R.S., Bayern-Quebec-Allianz to S.N., Deutsche Forschungsgemeinschaft (DFG) grant no. WA 2132/3-1 to B.W., and Fonds der Chemischen Industrie to C.W.

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Authors and Affiliations

  1. Biomedical Chemistry, Medical Research Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Carmen Wängler

  2. Department of Nuclear Medicine, Hospital of the Ludwig-Maximilians-University, Munich, Germany

    Carmen Wängler & Sabrina Niedermoser

  3. Department of Clinical Radiology and Nuclear Medicine, Molecular Imaging and Radiochemistry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Sabrina Niedermoser & Björn Wängler

  4. McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

    Joshua Chin, Katy Orchowski, Esther Schirrmacher, Alexey P Kostikov & Ralf Schirrmacher

  5. Lehrstuhl für Anorganische Chemie II, TU University of Dortmund, Dortmund, Germany

    Klaus Jurkschat & Liuba Iovkova-Berends

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  1. Carmen Wängler
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  4. Katy Orchowski
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Contributions

A.P.K., S.N., J.C., K.O., E.S., L.I.-B., K.J. and C.W. performed the experimental work. C.W., B.W. and R.S. wrote the manuscript.

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Correspondence to Carmen Wängler or Björn Wängler.

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Supplementary information

Supplementary Video 1

18F-labeling of peptides and proteins using the SiFA protocol, Part 1 (AVI 29017 kb)

Supplementary Video 2

18F-labeling of peptides and proteins using the SiFA protocol, Part 2 (AVI 32890 kb)

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Wängler, C., Niedermoser, S., Chin, J. et al. One-step 18F-labeling of peptides for positron emission tomography imaging using the SiFA methodology. Nat Protoc 7, 1946–1955 (2012). https://doi.org/10.1038/nprot.2012.109

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